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The first drug to show signs of not just halting multiple sclerosis (MS), but actually reversing the nerve damage caused by the condition, has taken a significant step towards clinical approval.

The results of a phase III trial, presented on 22 October at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, in Amsterdam, found that 78% of patients treated with the monoclonal antibody alemtuzumab remained free from relapse after two years — and half the relapse rate of one of the standard therapies, interferon β-1a (marketed as Rebif, among other names).

However, alemtuzumab did not perform quite as well as it had in earlier trials1. There was some evidence that it had reversed damage to nerves, but the result was not statistically significant, says Alasdair Coles, a neuroscientist at the University of Cambridge, UK, and the UK chief investigator of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I trial.

Coles told the meeting that magnetic resonance imaging showed that subjects taking alemtuzumab had also lost less brain volume than those taking Rebif, a proxy measure for overall tissue damage. "Alemtuzumab has eliminated the loss of brain tissue," he says.

Just 8% of patients taking alemtuzumab experienced a worsening in disability according to standard measures, in comparison with 11% taking Rebif. There was no statistical difference between the two groups, but Coles puts this down to Rebif performing better than expected. "The patients recruited in this trial showed very little worsening of disability," he says.

Significant promise?

Ludwig Kappos, chair of neurology at the University Hospital of Basel in Switzerland, who has been involved in several MS drug trials, says he is disappointed that there was no significant effect on disability progression. "This is in contrast to what the phase II study has shown," he says. But he expects this effect to show up in another ongoing phase III trial: CARE-MS II, the preliminary results of which should be available later this year.

There is no cure for MS, a condition caused by the body's own immune system attacking the myelin sheath that normally protects the nerves and speeds up neurological signals in the brain and spinal cord. At the moment, the only treatments are drugs such as interferon β-1a and glatiramer acetate (Copaxone), both of which merely slow the progression of the disease. <edit: the author missed a few here>

But alemtuzumab has the potential to reverse it: the drug tackles the mechanisms that cause damage to cells by effectively resetting the immune system. It targets the CD52 glycoproteins on the surface of mature immune cells, or lymphocytes, depleting levels of the aggressive T and B cells without affecting other lymphocytes. For reasons still not quite understood, when the lymphocytes repopulate, those involved in attacking the myelin sheath seem less likely to recover2.

Immune response

Although the efficacy of alemtuzumab is impressive, performance was never really the issue, says Les Funtleyder, a health-care strategist at trading firm Miller Tabak + Co in New York. "With alemtuzumab the issue is safety," he says.

The drug brings an increased risk of autoimmune diseases. In the trial, 18.1% of people taking alemtuzumab experienced thyroid-related autoimmune responses, and 0.8% developed the potentially life-threatening condition immune thrombocytopenia. But, says Coles, these findings mirror those from earlier trials, and it is possible to identify those patients most at risk by screening for certain biomarkers. "What's reassuring with this trial is that there are no new safety issues," he says.

Some patients and clinicians who have already got wind of the alemtuzumab's efficacy seem unwilling to wait for clinical approval, says Coles. The drug is already approved in many countries as a treatment for some forms of leukaemia and lymphoma, under the name Campath. In some countries, including the United Kingdom, it is legal to prescribe any drug for off-label use, and so patients have already started using it to treat MS, he says.

But it is not just MS patients who have been holding their breath over this drug, says Funtleyder. Earlier this year, Genzyme, a drug company based in Cambridge, Massachusetts, that makes alemtuzumab and a range of other therapies, was acquired by Paris-based drug-maker Sanofi. The value of the deal for Genzyme's shareholders is contingent on the success of alemtuzumab in treating MS; the first milestone is for the drug to gain approval from the US Food and Drug Administration before the end of March 2014.

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